scholarly journals BS17 RNA binding protein multiple splicing (RBPMS) drives a contractile splicing network in human embryonic stem cell derived vascular smooth muscle cells

Author(s):  
Aishwarya Jacob ◽  
Sanjay Sinha ◽  
Chris Smith
Cell Reports ◽  
2018 ◽  
Vol 24 (5) ◽  
pp. 1176-1189 ◽  
Author(s):  
Allison B. Herman ◽  
Christine N. Vrakas ◽  
Mitali Ray ◽  
Sheri E. Kelemen ◽  
Michael J. Sweredoski ◽  
...  

Stem Cells ◽  
2012 ◽  
Vol 30 (3) ◽  
pp. 452-460 ◽  
Author(s):  
Elisa Närvä ◽  
Nelly Rahkonen ◽  
Maheswara Reddy Emani ◽  
Riikka Lund ◽  
Juha-Pekka Pursiheimo ◽  
...  

2005 ◽  
Vol 280 (24) ◽  
pp. 22819-22826 ◽  
Author(s):  
Rudolf Pullmann ◽  
Magdalena Juhaszova ◽  
Isabel López de Silanes ◽  
Tomoko Kawai ◽  
Krystyna Mazan-Mamczarz ◽  
...  

2015 ◽  
Vol 465 (2) ◽  
pp. 185-194 ◽  
Author(s):  
Biraja C. Dash ◽  
Zhengxin Jiang ◽  
Carol Suh ◽  
Yibing Qyang

Vascular smooth muscle cells (VSMCs) play a major role in the pathophysiology of cardiovascular diseases. The advent of induced pluripotent stem cell (iPSC) technology and the capability of differentiating into virtually every cell type in the human body make this field a ray of hope for vascular regenerative therapy and understanding of the disease mechanism. In the present review, we first discuss the recent iPSC technology and vascular smooth muscle development from an embryo and then examine different methodologies to derive VSMCs from iPSCs, and their applications in regenerative therapy and disease modelling.


2006 ◽  
Vol 290 (1) ◽  
pp. R50-R56 ◽  
Author(s):  
Sunghou Lee ◽  
Hong Ji ◽  
Zheng Wu ◽  
Wei Zheng ◽  
Ali Hassan ◽  
...  

The current study examined angiotensin receptor (ATR) regulation in proliferating rat aortic vascular smooth muscle cells (VSMCs) in culture. Radioligand competition analysis coupled with RNase protection assays (RPAs) revealed that angiotensin type 1a receptor (AT1aR) densities (Bmax) increased by 30% between 5 and 7 days in culture [Bmax (fmol/mg protein): day 5, 379 ± 8.4 vs. day 7, 481 ± 12, n = 3, P < 0.05] under conditions in which no significant changes in AT1aR mRNA expression occurred [in RPA arbitrary units (AU): day 5, 0.23 ± 0.01 vs. day 7, 0.24 ± 0.04, n = 4] or in mRNA synthesis determined by nuclear run-on assays [AU: day 5, 0.35 ± 0.14 vs. day 7, 0.33 ± 0.11, n = 5]. In contrast, polysome distribution analysis indicated that AT1aR mRNA was more efficiently translated in day 7 cells compared with day 5 [% of AT1aR mRNA in fraction 2 out of total AT1R mRNA recovered from the sucrose gradient: day 5, 20.9 ± 9.9 vs. day 7, 56.8 ± 5.6, n = 3, P < 0.001]. Accompanying the polysome shift was 50% less RNA-protein complex (RPC) formation between VSMC cytosolic RNA binding proteins in day 7 cells compared with 5-day cultures and the 5′ leader sequence (5′LS) of the AT1aR [5′LS RPC (AU): day 5, 0.62 ± 0.15 vs. day 7, 0.23 ± 0.03; n = 4, P < 0.05] and also with exon 2 [Exon 2 RPC (AU): day 5, 35.0 ± 5.7 vs. day 7, 17.2 ± 3.6; n = 4, P < 0.05]. Taken together, these results suggest that AT1aR expression is regulated by translation during VSMC proliferation in part by RNA binding proteins that interact within exon 2 in the 5′LS of the AT1aR mRNA.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Roya Hakimjavadi ◽  
Denise Burtenshaw ◽  
Emma Fitzpatrick ◽  
Mariana Di Luca ◽  
Gillian Casey ◽  
...  

Data support a role for stem cell-derived vascular smooth muscle cells (SMC) in arteriosclerosis. Epigenetics play a critical role in SMC differentiation where histone proteins associated with the myosin heavy chain (Myh11) promoter are post-translationally modified by dimethylation of lysine 4 on histone 3 (H3K4me2). Studies report that ‘de-differentiated’ SMC do not exhibit loss of H3K4me2 at the Myh11 promoter even when mRNA levels decrease thereby allowing this modification to be used to track differentiated SMC. Our aim was to determine the level of H3K4me2 and H3K27me3 methylation of differentiated SMCs and compare to resident vascular stem cells and stem cell-derived SMC. Murine adventitial Sca1 + stem cells (APCs), rat medial Sox10 + multipotent vascular stem cells (MVSCs) and CD44 + bone-marrow derived mesenchymal stem cells (MSCs) were all examined for methylation of lysine 4 (H3K4me2) and lysine 27 (H3K27me3) on histone 3 associated with the Myh11 promoter, before and after SMC differentiation and compared to fresh aortic differentiated SMC and sub-cultured de-differentiated SMC in vitro by Chromatin Immunoprecipitation (ChIP) assay. Cells were also examined for Myh11 expression, stemness (telomerase activity) and multipotentcy. Differentiated rat and murine SMC were enriched for H3K4Me2 at the Myh11 promoter, compared to H3K27me3. Phenotypically de-differentiated sub-cutured rat and murine SMC were enriched for H3K4Me2 when compared to H3K27me3, but to a much lesser extent when compared to differentiated aortic SMC. In contrast, resident APCs and MVSCs, and bone-marrow derived MSCs, were all enriched for H3K27me3, concomitant with significant telomerase activity and multipotent differentiation capacity. The levels of enrichment of H3K27me3 dropped significantly after SMC differentiation with TGF-βeta1 concomitant with a significant enrichment of H3K4me2 to levels that mimicked the level of enrichment in de-differentiated SMC when compared to aortic differentiated SMC. De-differentiated SMC exhibit reduced enrichment of H3K4me2 at the Myh11 promoter region when compared to differentiated aortic SMCs, but mimic the level of enrichment of H3K4me2 observed following resident vascular stem cell differentiation to SMCs.


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